Sperm parameters in Israeli transgender women before and after cryopreservation.

BACKGROUND: The application of fertility preservation, initially intended for oncological patients prior to gonadotoxic treatment, has extended in recent years to transgender and gender-non-conforming individuals undergoing therapy for gender compatibility. OBJECTIVES: To examine semen quality and survival in transgender women pursuing semen cryopreservation in the presence or absence of gender-affirming hormonal medication. MATERIALS AND METHODS: In this retrospective cohort study, we reviewed data of 74 consecutive transgender women presenting for semen cryopreservation at a single center between 2000 and 2019. Semen parameters before and after cryopreservation were compared to a control group composed of 100 consecutive sperm bank donor candidates. A subgroup analysis of subjects who had used gender-affirming hormonal treatment was also performed. RESULTS: Compared to the control group, transgender women had lower total sperm count (144.0 vs. 54.5 million, respectively, p < 0.001), lower sperm motility percentage (65.0% vs. 51.0%, respectively, p < 0.001), and lower total motile sperm count (94.0 vs. 27.0 million, respectively, p < 0.001). Values were further decreased in transgender women who had received hormonal treatment before sperm cryopreservation. Post-thawing motility rate remained lower in the transgender group compared to the control group (20.0% vs. 45.0%, respectively, p < 0.001), and the total motile count remained lower as well (2.7 vs. 9.0 million, respectively, p < 0.001). Following sperm cryopreservation, the post-thaw decreases in total motile sperm count were higher in the transgender group compared with the control group (91.5% vs. 90.0%). Further subdivision in the transgender group showed that the decrease in total motile sperm count was lower for transgender women who did not use gender-affirming hormonal treatment compared to those who did (-89.7% vs. -92.6%, respectively, p < 0.01). DISCUSSION AND CONCLUSION: Sperm parameters in transgender women are poor compared to candidates for sperm donation representing the general population. Specimens collected after discontinuation of gender-affirming hormone treatments were further impaired. Moreover, post-thawing sperm total motile count, motility, and overall sperm survival were reduced in transgender women.

Covid-19 vaccination BNT162b2 temporarily impairs semen concentration and total motile count among semen donors.

BACKGROUND: The development of covid-19 vaccinations represents a notable scientific achievement. Nevertheless, concerns have been raised regarding their possible detrimental impact on male fertility OBJECTIVE: To investigate the effect of covid-19 BNT162b2 (Pfizer) vaccine on semen parameters among semen donors (SD). METHODS: Thirty-seven SD from three sperm banks that provided 216 samples were included in that retrospective longitudinal multicenter cohort study. BNT162b2 vaccination included two doses, and vaccination completion was scheduled 7 days after the second dose. The study included four phases: T0 - pre-vaccination baseline control, which encompassed 1-2 initial samples per SD; T1, T2 and T3 - short, intermediate, and long terms evaluations, respectively. Each included 1-3 semen samples per donor provided 15-45, 75-125 and over 145 days after vaccination completion, respectively. The primary endpoints were semen parameters. Three statistical analyses were conducted: (1) generalized estimated equation model; (2) first sample and (3) samples' mean of each donor per period were compared to T0. RESULTS: Repetitive measurements revealed -15.4% sperm concentration decrease on T2 (CI -25.5%-3.9%, p = 0.01) leading to total motile count 22.1% reduction (CI -35% - -6.6%, p = 0.007) compared to T0. Similarly, analysis of first semen sample only and samples' mean per donor resulted in concentration and total motile count (TMC) reductions on T2 compared to T0 - median decline of 12 million/ml and 31.2 million motile spermatozoa, respectively (p = 0.02 and 0.002 respectively) on first sample evaluation and median decline of 9.5 × 106 and 27.3 million motile spermatozoa (p = 0.004 and 0.003, respectively) on samples' mean examination. T3 evaluation demonstrated overall recovery without. Semen volume and sperm motility were not impaired. DISCUSSION: This longitudinal study focused on SD demonstrates selective temporary sperm concentration and TMC deterioration 3 months after vaccination followed by later recovery verified by diverse statistical analyses. CONCLUSIONS: Systemic immune response after BNT162b2 vaccine is a reasonable cause for transient semen concentration and TMC decline. Long-term prognosis remains good.

Assessing the quality of decision-making for planned oocyte cryopreservation.

PURPOSE: This survey study aims to examine the quality of planned oocyte cryopreservation (POC) decision-making in the domains of decision change, decision difficulty, decision regret and informed choice. METHODS: Of the 224 women who completed at least one POC cycle between 2012 and 2018 at a Canadian academic IVF centre, 198 were reachable by email for anonymous survey participation. RESULTS: Ninety-eight questionnaires were returned (response rate 49.5%). Of these, 86 fully completed questionnaires were analyzed for this study. Eighty-eight percent of respondents stated that it was a 'good decision' to cryopreserve oocytes, in retrospect. Despite this, 31% found the decision-making process to be 'difficult'. Three in five (61%) would have made 'exactly the same' decision without any change, yet slightly over a third (35%) would have made a 'similar' decision, but with option-related changes and process-related changes. A negative correlation between 'decision regret' and 'informed choice' was found (p < .005). Those who stated that they would have made exactly the 'same' POC decision were found to have a significantly higher 'informed choice' score compared to others who would have made a 'similar' or 'completely different' decision, in retrospect (p < .001). Respondents with lesser 'decision regret' were significantly more likely to appraise their decision as a well-informed choice (p < .001). CONCLUSIONS: Our findings show that high-quality POC decision-making is accompanied by the perception of being able to make an informed choice, which can be achieved by providing patients with adequate information and individualized counselling to help patients set realistic expectations of cycle outcomes.

Human umbilical cord perivascular cells prevent chemotherapeutic drug-induced male infertility in a mouse model.

OBJECTIVE: To study whether intratesticular (IT) administration of 2 sources of human umbilical cord perivascular cells (HUCPVC), rich and potent sources of mesenchymal stromal cells (MSC), before chemotherapy can prevent infertility in a mouse model. DESIGN: Two control groups of CD1 male mice without busulfan (BUS) administration (untreated and IT media injection groups) were included. Experimental groups included IT administration of media, first trimester (FTM) HUCPVCs or term HUCPVCs (n = 5 each) injected 3 days before BUS treatment (20 mg/kg). All groups were included in a mating time course study over 6 months. SETTING: Preclinical study in a fertility center research laboratory. PATIENTS: Not applicable. INTERVENTION: IT delivery of FTM or term HUCPVC before BUS treatment. MAIN OUTCOME MEASURES: Pregnancies, litter sizes, and gross morphology of offspring were monitored. Caudal epididymal sperm concentration, motility, and progressive motility were assessed by computer-assisted sperm analysis. Spermatogenesis was also assessed histologically in testicular tissue sections. RESULTS: FTM and term HUCPVC displayed an MSC-associated immunophenotype and expressed transcripts encoding paracrine factors known to regulate the testicular cell niche. IT administration of FTM and term HUCPVC before chemotherapy promoted the recovery of spermatogenesis and fertility compared with BUS-treated animals that received a media injection. Although the total number of pups sired over 6 months by males treated with FTM or term HUCPVC was reduced compared with untreated or media-injected controls, litter size and sperm parameters in fertile animals did not differ between control and cell-treated groups. CONCLUSION: HUCPVC represent a promising source of MSC-based therapy to prevent gonadotoxic chemotherapeutic drug-induced infertility.

Is there an association between paternal age and aneuploidy? Evidence from young donor oocyte-derived embryos: a systematic review and individual patient data meta-analysis.

BACKGROUND: Delayed parenthood, by both women and men, has become more common in developed countries. The adverse effect of advanced maternal age on embryo aneuploidy and reproductive outcomes is well known. However, whether there is an association between paternal age (PA) and embryonic chromosomal aberrations remains controversial. Oocyte donation (OD) is often utilized to minimize maternal age effects on oocyte and embryo aneuploidy, thus providing an optimal model to assess the effect of PA. Several studies have revealed a higher than expected rate of aneuploidy in embryos derived from young oocyte donors, which warrants examination as to whether this may be attributed to advanced PA (APA). OBJECTIVE AND RATIONALE: The objective of this systematic review and individual patient data (IPD) meta-analysis is to evaluate existing evidence regarding an association between PA and chromosomal aberrations in an OD model. SEARCH METHODS: This review was conducted according to PRISMA guidelines for systematic reviews and meta-analyses. Medline, Embase and Cochrane databases were searched from inception through March 2020 using the (MeSH) terms: chromosome aberrations, preimplantation genetic screening and IVF. Original research articles, reporting on the types and/or frequency of chromosomal aberrations in embryos derived from donor oocytes, including data regarding PA, were included. Studies reporting results of IVF cycles using only autologous oocytes were excluded. Quality appraisal of included studies was conducted independently by two reviewers using a modified Newcastle-Ottawa Assessment Scale. A one-stage IPD meta-analysis was performed to evaluate whether an association exists between PA and aneuploidy. Meta-analysis was performed using a generalized linear mixed model to account for clustering of embryos within patients and clustering of patients within studies. OUTCOMES: The search identified 13 032 references, independently screened by 2 reviewers, yielding 6 studies encompassing a total of 2637 IVF-OD cycles (n = 20 024 embryos). Two 'low' quality studies using FISH to screen 12 chromosomes on Day 3 embryos (n = 649) reported higher total aneuploidy rates and specifically higher rates of trisomy 21, 18 and 13 in men ≥50 years. One 'moderate' and three 'high' quality studies, which used 24-chromosome screening, found no association between PA and aneuploidy in Day 5/6 embryos (n = 12 559). The IPD meta-analysis, which included three 'high' quality studies (n = 10 830 Day 5/6 embryos), found no significant effect of PA on the rate of aneuploidy (odds ratio (OR) 0.97 per decade of age, 95% CI 0.91-1.03), which was robust to sensitivity analyses. There was no association between PA and individual chromosome aneuploidy or segmental aberrations, including for chromosomes X and Y (OR 1.06 per decade of age, 95% CI 0.92-1.21). Monosomy was most frequent for chromosome 16 (217/10802, 2.01%, 95% CI 1.76-2.29%) and trisomy was also most frequent for chromosome 16 (194/10802, 1.80%, 95% CI 1.56-2.06%). WIDER IMPLICATIONS: We conclude, based on the available evidence, that APA is not associated with higher rates of aneuploidy in embryos derived from OD. These results will help fertility practitioners when providing preconception counselling, particularly to older men who desire to have a child.

A comprehensive review of the impact of COVID-19 on human reproductive biology, assisted reproduction care and pregnancy: a Canadian perspective.

Currently, the world is in the seventh month of the COVID-19 pandemic. Globally, infections with novel SARS-CoV-2 virus are continuously rising with mounting numbers of deaths. International and local public health responses, almost in synchrony, imposed restrictions to minimize spread of the virus, overload of health system capacity, and deficit of personal protective equipment (PPE). Although in most cases the symptoms are mild or absent, SARS-CoV-2 infection can lead to serious acute respiratory disease and multisystem failure. The research community responded to this new disease with a high level of transparency and data sharing; with the aim to better understand the origin, pathophysiology, epidemiology and clinical manifestations. The ultimate goal of this research is to develop vaccines for prevention, mitigation strategies, as well as potential therapeutics.The aim of this review is to summarize current knowledge regarding the novel SARS CoV-2, including its pathophysiology and epidemiology, as well as, what is known about the potential impact of COVID-19 on reproduction, fertility care, pregnancy and neonatal outcome. This summary also evaluates the effects of this pandemic on reproductive care and research, from Canadian perspective, and discusses future implications.In summary, reported data on pregnant women is limited, suggesting that COVID-19 symptoms and severity of the disease during pregnancy are similar to those in non-pregnant women, with pregnancy outcomes closely related to severity of maternal disease. Evidence of SARS-CoV-2 effects on gametes is limited. Human reproduction societies have issued guidelines for practice during COVID-19 pandemic that include implementation of mitigation practices and infection control protocols in fertility care units. In Canada, imposed restrictions at the beginning of the pandemic were successful in containing spread of the infection, allowing for eventual resumption of assisted reproductive treatments under new guidelines for practice. Canada dedicated funds to support COVID-19 research including a surveillance study to monitor outcomes of COVID-19 during pregnancy and assisted reproduction. Continuous evaluation of new evidence must be in place to carefully adjust recommendations on patient management during assisted reproductive technologies (ART) and in pregnancy.

Is there a correlation between paternal age and aneuploidy rate? An analysis of 3,118 embryos derived from young egg donors.

OBJECTIVE: To investigate a possible correlation between chromosomal aberrations and paternal age, analyzing embryos derived from young oocyte donors, with available preimplantation genetic testing for aneuploidy results from day 5/6 trophectoderm biopsy obtained by next-generation sequencing for all 24 chromosomes. DESIGN: Retrospective cohort study. SETTING: Canadian fertility centre. PATIENT(S): A total of 3,118 embryos from 407 male patients, allocated into three paternal age groups: group A, ≤39 years (n = 203); group B, 40-49 years (n = 161); group C, ≥50 years (n = 43). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary outcomes were aneuploidy, euploidy, mosaicism, and blastocyst formation rates. Secondary endpoints were comparison of specific chromosome aneuploidy, segmental and complex (involving two chromosomes + mosaicism >50%) aneuploidy, and analysis of overall percentage of chromosomal gains and losses within each group. RESULT(S): The study included 437 in vitro fertilization (IVF) antagonist cycles using 302 oocyte donors in which preimplantation genetic testing for aneuploidy was performed. Overall, 70.04% of embryos were euploid, 13.9% were aneuploid, and 16.06% were mosaic. No significant differences among paternal age groups A, B, and C were found in euploidy rates (69.2%, 70.6%, 71.4%, respectively), aneuploidy rates (14.7%, 12.8%, 13.9%, respectively) or mosaicism rates (16.1%, 16.6%, 13.6%; respectively). The fertilization rate was lower in group C compared with group B (76.35% vs. 80.09%). No difference was found in blastocyst formation rate between the study groups (median 52% [interquartile range, 41%, 67%] vs. 53% [42%, 65%] vs. 52% [42%, 64%], respectively). A generalized linear mixed model regression analysis for embryo ploidy rates found older oocyte donor age to be independently associated with embryo aneuploidy (odds ratio = 1.041; 95% CI, 1.009-1.074). The rate of segmental aneuploidies was significantly higher in the older versus younger paternal age group (36.6% vs. 19.4%). CONCLUSION(S): No association was found between paternal age and aneuploidy rates in embryos derived from IVF cycles using young oocyte donors, after adjusting for donor, sperm, and IVF cycle characteristics. Advanced paternal age ≥ 50, compared with younger paternal ages, was associated with a lower fertilization rate and increased rate of segmental aberrations.

The Effect of Advanced Maternal Age on Embryo Morphokinetics.

Purpose: To compare the morphokinetic parameters of pre-implantation development between embryos of women of advanced maternal age (AMA) and young women. Methods: Time-lapse microscopy was used to compare morphokinetic variables between 495 embryos of AMA women ≥ age 42 years and 653 embryos of young patients ( 0.05). Conclusions: While early morphokinetic parameters do not reflect dynamics unique to embryos of older women, a tendency toward developmental arrest was observed, which would likely be even more pronounced at later stages of development.

Morphokinetic characteristics of embryos originating from extremely small follicles: A prospective study.

OBJECTIVE: To investigate the developmental potential of oocytes and embryos derived from extremely small follicles (<10 mm) in comparison to those originated in larger follicles. STUDY DESIGN: A prospective study, undertaken in a university affiliated single center tertiary hospital. The study included 98 patients undergoing infertility treatments. On the day of ovum pickup (OPU) follicles were counted and measured. Aspiration of follicles larger and smaller than 10 mm was undertaken separately and the development of embryos originating from oocytes from these follicles was followed up using different wells for each embryo. There was no low limit of size for aspiration. Each oocyte retrieved was marked for its origin and numbered for further follow up. We recorded: Oocytes retrieved, maturation stage, fertilization rate, cleavage rate, morphokinetic parameters, embryo transfers, embryo freezing, oocyte freezing and biopsy rate for preimplantation genetic diagnosis (PGD). Quality was evaluated by the morphokinetic parameters of the embryos developed using time-lapse imaging technology. Day 3 KIDScore was calculated to all embryos. RESULTS: Small follicles compared to large follicles displayed lower recovery rate (45% vs. 74%, P < 0.0001), fewer matured oocytes (37.5% vs. 61.7%, P < 0.0001), higher rates of GV oocytes (20.7% vs., 3.7%, P < 0.0001), and lower fertilization rate (43.7% vs. 63.3%, P < 0.0001. However, morphokinetic variables were similar between embryos that originated from either small or large follicles. Median KIDscores were identical for embryos from small or large follicle origin. CONCLUSIONS: Embryos originated from small follicles were not different than embryos from larger follicles, as assessed by morphokinetic parameters in time lapse system. In view of our findings, physicians should bear in mind that small follicle aspiration might yield good quality embryos.

Advanced cervical dilatation and spontaneous preterm labor: a comparison between twin and singleton gestations.

OBJECTIVE: To determine the admission to delivery interval and the rate of immediate delivery in twin versus singleton gestation complicated by spontaneous preterm labor (SPTL). METHODS: A retrospective cohort study of pregnant women presenting with advanced cervical dilatation of 3-5 cm and frequent uterine contractions at 24-34 weeks of gestation was performed. The rate of progression to delivery within 12 h and 24 h, as well as rates of prolonged latency, were compared between twins and singletons gestations. RESULTS: Sixty-nine women were included, of which 25 carried twins and 44 singletons. The overall rate of spontaneous delivery within 12 h and 24 h was 47.8% and 59.4%, respectively, and similar between twins and singletons. Nevertheless, prolonged latency of 10 days or more after presentation was more frequent among twins compared with singletons [10/25 (40%) vs. 7/44 (15.9%), respectively; P=0.026]. Moreover, women carrying twins presenting with advanced cervical dilatation had a better chance of completing a full 2-dose antenatal betamethasone course compared with singletons [19/25 (76%) of twins compared with 21/44 (47.7%) of singletons, odds ratio 3.5, 95% confidence interval 1.16-10.34; P=0.022]. CONCLUSION: Up to 60% of women presenting with advanced cervical dilatation prior to 34 weeks' gestation give birth within 24 h. Nevertheless, women carrying twins have a better chance of completing a betamethasone course and having prolonged latency compared with singletons.

The 'immunologic theory' of preeclampsia revisited: a lesson from donor oocyte gestations.

OBJECTIVE: To determine the prevalence of placental complications in patients conceived through donor versus autologous oocytes. STUDY DESIGN: A retrospective cohort study including 2 groups of patients who conceived through in vitro fertilization using: (1) donor oocyte (n = 139) and (2) autologous oocyte (n = 126). Only singleton gestations were included. The rate of placental complications including preeclampsia, gestational hypertension, and intrauterine growth restriction was compared between these 2 groups. RESULTS: The women who conceived using donor oocytes were older compared with women who conceived using autologous oocytes (median maternal age 45 vs 41, P < .01). The rate of hypertensive diseases of pregnancy including gestational hypertension and preeclampsia was significantly higher in ovum donor recipients compared with women conceived with autologous oocytes (25% vs 10%, P < .01). Similarly, the rate of intrauterine growth restriction was also higher among patients conceived through oocyte donation although it did not reach statistical significance (9.3% vs 4%, P = .08). When maternal age was restricted to ≤45 years, the rate of hypertensive diseases of pregnancy remained significantly higher among ovum donor compared with autologous oocyte recipients (22% vs 10%, P = .02). Adjustment for maternal age, gravidity, parity, and chronic hypertension revealed that oocyte donation was independently associated with higher rate of hypertensive diseases of pregnancy (P = .01). CONCLUSION: Patients conceived through oocyte donation have an increased risk for placental complications of pregnancy. These findings support the 'immunologic theory' suggesting that immunologic intolerance between the mother and the fetus may play an important role in the pathogenesis of preeclampsia.

Increased matrix metalloproteinases-1,-9 in the uterosacral ligaments and vaginal tissue from women with pelvic organ prolapse.

OBJECTIVES: To investigate the possible association of increased matrix metalloproteinases (MMPs)-1,-9 with pelvic organ prolapse (POP) and to evaluate whether inflammatory processes contribute to its development. STUDY DESIGN: Forty women who underwent hysterectomy, 20 with POP grade 2 and above, and 20 without POP, participated in the study. Biopsies from the uterosacral ligaments and vaginal mucosa were obtained from each woman. Each biopsy was sectioned and stained for MMP-1 and MMP-9 by immunohistochemical methods and with hematoxylin and eosin (H&E). MMP-1,-9 expressions were evaluated on the immunostained slides. H&E stained sections were examined for possible inflammatory changes. RESULTS: A higher stromal (extra-cellular) expression of MMPs-1,-9 was found in POP cases compared with controls in vaginal biopsies (MMP-1: p=0.004; MMP-9: p=0.042) as well as in uterosacral ligament biopsies (MMP-1: p=0.011; MMP-9: p=0.015). Increased intracellular expression of both MMPs was also demonstrated in fibroblasts in biopsies of women with POP (p<0.001 for all). Most of these differences persisted after controlling for age. The degree of inflammatory changes reflected by the number of lymphocytes, plasma cells and capillary-sized blood vessels per 10 high power fields, was similar in specimens obtained from women with and without POP. CONCLUSIONS: The expression of MMPs-1,-9 appears to be increased in tissues from women with POP. This supports an association, although not a causal relation, between increased MMPs-1,-9 and POP. Inflammation does not seem to play an important role in the pathogenesis of POP.